Neurotoxicity of Organochlorine Compounds

Pesticides such as dichlorodiphenyltrichloroethane (DDT), endrin, dieldrin, aldrin, endosulfan, chlordane, heptachlor, lindane, and chlordecone have been in use since the late 1940s and are readily available, in most countries, to be used alone or in combination with other pesticides as sprays, powders, pellets, and dusts (see Chapter 13). These are lipophilic compounds and many of them have been demonstrated to form depots in tissues with high lipid content, especially the brain. This specific chemistry of organoclorines makes serum level measurements uninformative, as severe toxicity has been documented in patients with low serum levels as a result of chronic exposure and sequestration of the toxin in the organism. Most of these compounds (cyclo-dienes, hexachlorocyclohexanes, and toxaphene organochlorines) inhibit the Y-aminobutyric acid (GABA) receptors and prevent chloride influx in the CNS, resulting in a typical "GABA-ergic" clinical picture of agitation, confusion, and seizures (40-42).

Organochlorines are divided into highly toxic (aldrin, dieldrin, endrin [banned in the United States], and endosulfan) and moderately toxic (chlordane, DDT [banned in the United States], heptachlor, kepone, lindane, mirex, and toxaphene). There are no nontoxic organochlorine-based pesticides, and cumulative exposure to even moderately toxic agents may lead to severe disability (42).

In acute exposure, the onset of symptoms is abrupt and caused by CNS stimulation and lowering of the seizure threshold. Patients often develop nausea and vomiting, followed by confusion, tremors, coma, seizures, and respiratory depression. Fatality may occur within 4 to 8 hours and is primarily due to respiratory failure or seizures. Cerebral edema may occur and is viewed as a negative prognostic sign. Emergency treatment with cholestyra-mine has been associated with better prognosis and somewhat higher efficacy than the commonly used activated charcoal (these agents can be used concurrently). Induced diuresis, hemodialysis, and hemosorption with activated charcoal have not been shown to be effective in enhancing the elimination of the toxin (40,41).

Patients with long-term occupational exposure to organochlorine pesticides may develop a variety of nonspecific complaints including headaches, nausea, fatigue, muscle twitching, and visual disturbances. There is no reliable statistical data associating exposure to organochlorines with any specific type or location of cancer. Some of the less obvious signs of cumulative tox-icity of these chemicals include paresthesias of the face, auditory or visual hallucinations, and perceptual disturbances, although the latter are more reliably associated with acute toxicity (41-44).

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